1. Field of the Invention
The present convention concerns a new and improved membrane to be used for testing the diffusion of a substance through said membrane, and in particular for simulating the absorption--by an organism--of an active and/or auxiliary substance contained in a medicine, or of a cosmetic substance, or of a substance to be used in the treatment of plants. The substance may consist of a chemical element or a chemical compound or of a mixture of two or more elements and/or compounds. The invention also concerns a system and a process for testing the diffusion of a substance through said membrane, as well as a method for making the membrane. The invention is to fulfill a need in the fields of physiological and pharmacological research, primarily but not exclusively in conjunction with the absorption of pharmaceuticals by the body of living organisms.
Active substances of orally administered medicines are normally absorbed by the biophase of the respective human or animal by way of the mucous membranes of the stomach and/or the intestines. This absorption takes place at least partially by diffusion. Information regarding the details of the absorption process is of great interest to researchers doing physiological research and/or development and testing of pharmacological products. In order to keep the number of required tests on living organisms low, it is desirable to simulate the absorption in vitro, i.e. outside the body of the living human or animal. Similar problems arise for example if the absorption behavior of the skin covering the body is to be tested with respect to active substances contained in ointments, or with respect to components of cosmetic products. Furthermore, knowledge referring to the absorption behavior of plants is of use, as are treated for example with plant protective chemicals and fertilizers and by necessity absorb substances contained therein, both desirable and undesirable.
2.Description of the Prior Art
In the publication titled "Theoretical and Experimental Studies of Transport of Micelle-Solubilized Solutes" by G. E. Amidon, W. I. Higuchi and N. F. H. Ho as appeared in the Journal of Pharmaceutical Sciences, Vol. 71, 1982, page 77, is disclosed a method performed by means of a system comprising a rotor adapted to be rotated around a vertical axis and comprising a sleeve-shaped wall member. An opening is provided at the lower end of said wall member to make it possible--by means of a clamping sleeve screwed onto the wall member--to fixedly mount two spacer rings, a perforated supporting plate and a lipid-like membrane consisting of dimethylpolysiloxane at said lower end, so that said lipid-like membrane, together with said wall member, will bound a compartment and separate the same from another compartment. Since the membranes used in this known system possess properties greatly deviating from the properties of natural mucous membranes of the stomach and the intestines, it is highly questionable whether the results of the tests performed with said system can be transferred to actual absorption processes as take place in the living organism. If the membranes are lipid-like--particularly when testing substances highly soluble in fat--the danger exists, that these substances will accumulate primarily in the membranes, and the membranes will only inadequately simulate the absorption process through living biomembranes. As a matter of fact, when the membranes are genuine, i.e. living biomembranes, the substances may undergo chemical changes, i.e. they may become metabolized. Furthermore, the fact, that the membrane region in which substance diffusion is possible, is subdivided into relatively small circular subzones by sections provided between the holes of the supporting plate, may cause some problems. Furthermore, it appears to be comparatively troublesome in this known system to first have to temporarily unscrew the clamping sleeve and then fixedly mount the membrane between the supporting plate and one of the spacer rings by screwing the clamping sleeve back in place, and then to separate the membrane again from the wall member after completion of the test.